DESCRIPTION: The principal investigator notes that in recent years he has been actively involved in developing efficient and regiocontrolled syntheses for pyrrole containing substances which have subsequently been bioassayed as part of the National Cancer Institute's in vitro screening program and that these synthetic methods have been based on the condensation reactions of vinylogous iminium salt derivatives with alpha-aminocarbonyl compounds. He indicates that as part of this program, he is currently directing his efforts towards a new and novel, marine derived alkaloid, Rigidin which has been shown to be a significant inhibitor of Calmodulin activated phosphodiesterase, a possible chemotherapeutic target. In this proposal he states that he seeks to accomplish at least four things: 1. extend the chemistry that he has developed for the regiocontrolled preparation of disubstituted pyrroles to the synthesis of trisubstituted pyrroles. 2. carry out appropriate experiments to understand the controlling features for the formation of trisubstituted pyrroles from a variety of vinylogous iminium salt derivatives. 3. to begin to apply this chemistry to the synthesis of the novel, Calmodulin antagonist Rigidin and related substances such as the bioactive, natural product Polycitone A. 4. to continue to submit samples of Rigidin and Polycitone A analogs, precursors and related pyrrole containing compounds to the NCI for further biological evaluation as part of the in vitro, primary antitumor screening program.